Dopaminergic Modulation of Dynamic Emotion Perception.

Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson's disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioral modulation. Interestingly, while a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. A total of 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo. To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing. Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition. Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing. Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition.SIGNIFICANCE STATEMENT A high prevalence of emotion recognition difficulties among clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes. However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights. The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition. Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.

Addictions in patients with atopic dermatitis: a cross-sectional pilot study in Germany.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide and displays many atopic, but also non-atopic comorbidities. Among the latter, mental health disorders such as depression have been extensively studied. However, data on addictions are still rare. OBJECTIVES: The aim of this study was to assess the prevalence of different kinds of addictions in adult AD patients using a single-centre approach. METHODS: This non-interventional cross-sectional study was performed from 03/2020 to 05/2020 at the Department of Dermatology of a large German university hospital. Participants with a diagnosis of AD confirmed by a dermatologist answered questions about disease severity (patient-oriented eczema measure, POEM), quality of life (Dermatology Life Quality Index, DLQI) and smoking habits. They were screened for problematic alcohol consumption, drug abuse, internet addiction and pathological gambling using internationally established and validated questionnaires. RESULTS: 157 patients (56.1% female; mean age of 49.9 ± 20.4) with an average POEM of 13.7 ± 7.5 and DLQI of 6.1 ± 5.4 were evaluated. 14.1% were identified as regular smokers, 12.1% screened positive for alcohol dependency, 6.4% for drug use disorders, 4.5% for Internet addiction and 3.2% for pathological gambling. Co-occurrences of different addictions were observed, and a positive correlation was noted between DLQI scores and smoking. CONCLUSIONS: In summary, this study hints at elevated positive screening rates for problematic alcohol consumption, drug use disorders, Internet addiction and problem gambling compared with the general population. Screening routinely for addictions may improve patient-centred health care of AD patients.

Atopic dermatitis: disease characteristics and comorbidities in smoking and non-smoking patients from the TREATgermany registry.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. OBJECTIVES: In this study, AD characteristics and its atopic comorbidities are compared in smoking and non-smoking AD patients. METHODS: TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non-smokers. RESULTS: Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non-smokers, however, lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non-smoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than non-smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to non-smokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. CONCLUSIONS: German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Validation of ICD-11 PTSD and complex PTSD in foster children using the International Trauma Questionnaire.

OBJECTIVE: ICD-11 introduces post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD) as two distinct trauma-related disorders. Using the International Trauma Questionnaire (ITQ) as disorder-specific measure, this study is the first to examine the factorial and construct validity of ICD-11 PTSD, CPTSD and the ITQs' applicability in children. METHODS: Two hundred and eight Austrian foster children completed a set of standardized measures. Excluding participants who reported not having experienced any kind of trauma, a final sample of 136 children completed the ITQ. Factorial and construct validity of ICD-11 CPTSD and psychometric properties of ITQ scales were assessed by factor analysis and latent class analysis. RESULTS: Confirmatory factor analysis supported the two-factor higher-order model of ICD-11 CPTSD in children by high factor loadings and excellent model fit. Reliability and regression analysis evidenced psychometric adequacy and discriminant validity of ITQ scales. Latent class analysis substantiated construct validity of ICD-11 CPTSD, identifying a CPTSD (22.8%), PTSD (31.6%) and low symptoms class (45.6%). The CPTSD class showed highest rates of childhood trauma, comorbid psychopathology and functional impairment. CONCLUSION: Factorial and construct validity of ICD-11 CPTSD was evidenced in children for the first time using precise descriptions of ICD-11 symptom content, supporting the reliability and validity of the ITQ in children.

Happiness in dermatology: a holistic evaluation of the mental burden of skin diseases.

BACKGROUND: According to the World Health Organization, mental health is a state of well-being and not merely the absence of disease. However, studies exploring subjective well-being in patients with skin diseases are very rare. OBJECTIVES: To assess subjective well-being, i.e. 'happiness', in patients with different skin diseases and to compare them to other patient groups and healthy controls. METHODS: A cross-sectional study was conducted from 12/2017 to 04/2019. Patients receiving in- or outpatient care for psoriasis, atopic eczema, nummular eczema, mastocytosis, skin cancer (malignant melanoma and keratinocyte carcinoma), human immunodeficiency virus (HIV) or chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis) were recruited at two hospitals in Bavaria, Germany. Healthy individuals living in or near Munich served as a control group. All participants filled in a questionnaire assessing happiness, measured as positive affect (PA), negative affect and satisfaction with life (SWL; together representing subjective well-being) and a heuristic evaluation of one's own happiness. RESULTS: Data from 229 dermatologic patients (53.3 ± 18.5 years, 48% women), 49 patients with inflammatory bowel diseases (48.9 ± 18.7 years, 43% women), 49 patients with HIV (46 ± 10.1 years, 10% women) and 106 healthy controls (38.4 ± 13.4 years, 49% women) were analysed. Compared to the controls, dermatologic patients reported lower heuristic happiness (P = 0.023) and PA (P = 0.001) but higher SWL (P = 0.043). Patients with psoriasis and atopic eczema reported the lowest happiness, as they reported significantly lower PA (P = 0.032 and P < 0.001) and heuristic happiness (P = 0.002 and P = 0.015) than the control group. Patients with skin cancer reported higher SWL than the control group (P = 0.003). Dermatologic patients reported lower happiness than patients with HIV but reported greater happiness than patients with IBD. CONCLUSIONS: Dermatologic patients experience lower levels of happiness, especially PA, compared to healthy controls. As PA is linked to desirable health outcomes, targeting PA could be a promising holistic approach for the treatment of skin diseases.

The association between challenging behaviour and symptoms of post-traumatic stress disorder in people with intellectual disabilities: a Bayesian mediation analysis approach.

BACKGROUND: A preponderance of behavioural symptoms is assumed to be the main difference in the manifestation of symptoms of post-traumatic stress disorder (PTSD) in people with intellectual disability (ID). However, no study so far has assessed the relationship between challenging behaviour (CB) and PTSD. The present study aims to explore this relationship by exploring whether CB is directly related to trauma exposure or whether this relationship is mediated through core symptoms of PTSD. METHODS: Trauma exposure and current symptoms of PTSD were assessed in 43 adults with mild to moderate ID. Parallel versions were administered to 43 caregivers, including the Aberrant Behaviour Checklist to measure CB. Bayesian mediation analyses were conducted using self-rated and informant-rated data. RESULTS: The self-report data showed no associations of CB with trauma exposure or PTSD symptoms. The association between informant-rated trauma exposure and irritability was mediated by severity and frequency of PTSD symptoms. The associations between informant-reported trauma exposure and the Aberrant Behaviour Checklist subscales hyperactivity and inappropriate speech were mediated by PTSD symptom severity. CONCLUSIONS: The relationship between trauma exposure and CB was mediated by PTSD symptoms. PTSD core symptoms should be considered as underlying causes of CB, highlighting the necessity to explore trauma biography and symptoms of PTSD. The improvement of self-report assessment in people with ID is an important task for future studies.

[Medical apps-possibilities for pruritus]. / Medizinische Apps ­ Möglichkeiten bei Pruritus.

BACKGROUND: Apps have become part of our daily lives. Apps for pruritus could also play a role in the management of symptoms. AIM: The aim of this article is to review existing apps for pruritus. In addition, we will discuss whether these apps have been validated and how and which offers might still be lacking. MATERIALS AND METHODS: The two largest app stores as well as PubMed and Google were searched for apps regarding pruritus. Relevant medical apps were documented and categorized with respect to their functions. PubMed was searched to identify validation studies. RESULTS: In total 21 apps for pruritus were identified. Of those 12 explicitly focused on pruritus, while 8 included pruritus as a symptom of an underlying disease (especially eczema and urticaria). The following app categories were derived: medical history of chronic pruritus, assessment of pruritus in clinical trials, assessment of nocturnal pruritus, information about pruritus, and diseases with pruritus as a symptom. Three of the apps with explicit focus on pruritus have been scientifically validated. DISCUSSION: There are different apps for pruritus available. Most apps which explicitly focus on pruritus are aimed at physicians and scientists, while apps for diseases with pruritus as a symptom are more patient-centered. Due to technological advances, apps and wearables could improve management of pruritus in the future.

Primary prevention of keratinocyte carcinoma among outdoor workers, the general population and medical professionals: a systematic review updated for 2019.

Worldwide 2-3 million cases of keratinocyte carcinoma (KC) are diagnosed annually. Sun-related knowledge is essential for adequate protection against solar ultraviolet radiation (UVR), the main risk factor for KC. The goal was (i) to provide an updated overview of primary prevention against KC including skin cancer-related knowledge, attitudes and sun protection behaviour (SPB) of outdoor workers, the general population and medical professionals as well as (ii) to evaluate the effectiveness and acceptability of sun protection programmes. We conducted a systematic review of articles indexed for MEDLINE on PubMed using selected MeSH terms and keywords related to the studied topic as well as an extensive hand search of publications between 1 January 2012 and 31 December 2018. We identified 51 relevant cross-sectional studies and 22 interventional studies. Sun-related knowledge and attitude showed substantial differences with some alarming results, including people who had not even heard about skin cancer before. Reported SPB varied enormously between the included studies, with none of the studies providing an overall sufficient SPB in their examined sun protection measures. However, sun protection programmes using new technologies seem to have great potential to increase sun-related knowledge and SPB. In countries worldwide, particularly in those where KC is not yet a public health issue, UVR protection should be promoted by healthcare institutions and authorities, politicians, cancer foundations and dermatologists to increase awareness as well as SPB and to decrease the worldwide burden of KC.

Medical needs and major complaints related to pruritus in Germany: a 4-year retrospective analysis using Google AdWords Keyword Planner.

BACKGROUND: It is difficult to estimate the prevalence of acute and chronic pruritus in the population at large due to a lack of affected persons seeking medical assistance. OBJECTIVE: To discover the incidence of pruritus in Germany and determine what the most common related complaints are via an analysis of Google's search volume. METHODS: From June 2013 to April 2017, the Google AdWords Keyword Planner was utilized to select and critically assess relevant keywords for 'pruritus'. RESULTS: Among a total of 13 691 470 German language Google searches on the topic of pruritus, it was found that the most searched for terms included atopic eczema (24.3%) and the layman's term for psoriasis ('Schuppenflechte'; 17.8%), as well as just psoriasis (13.4%). 'Juckreiz', the German word for pruritus, was determined to be only the sixth most searched for term (2.9%). Anal pruritus and pruritus of the entire body comprised the most searched for localizations. The various factors that impact pruritus, particularly skin conditions and disorders, were established to be among the most searched for terms (72.6%). A decreased monthly search volume was associated with the changing seasons; the summertime had the lowest number of searches for pruritus. CONCLUSION: The Google search engine analysis provided insight for this study into the unexpectedly large number of unmet medical needs of those suffering from pruritus within Germany, especially that of specific localizations on the body.

[Pruritus in Germany-a Google search engine analysis]. / Pruritus in Deutschland ­ eine Google-Suchmaschinenanalyse.

BACKGROUND: Because affected persons often do not visit a doctor, the prevalence of chronic and acute pruritus in the general population is difficult to determine. OBJECTIVES: The aim of this study is to estimate the frequency and the most common locations of pruritus in German internet users, who-with 62.4 million persons-represent a large majority of the German population, by analysing the Google search volume. MATERIALS AND METHODS: Relevant keywords for the subject "pruritus" were identified and analysed using the Google AdWords Keyword Planner. The assessment period was January 2015 to December 2016. RESULTS: In total the Google AdWords Keyword Planner identified 701 keywords for the topic "Juckreiz" (German lay word for pruritus), resulting in 7,531,890 pruritus-related Google searches during the assessment period. Most common search terms were the German lay term for atopic eczema ("Neurodermitis", 23.7%), the German lay term for psoriasis ("Schuppenflechte", 17.8%) and "psoriasis" (13%). The German lay term for pruritus ("Juckreiz") was only the sixth most searched term (3%). Most searches (72%) focused on influencing factors for pruritus, especially on skin diseases and skin conditions. The most commonly searched location was pruritus on the whole body, followed by anal pruritus. Analysis of the temporal course showed a higher monthly search volume during winter. CONCLUSION: With its unconventional methodology, a Google search engine analysis, this study allows a rough estimation of the medical need of pruritus in the German general population, which seems to be higher than expected. Especially pruritus in the anal area was identified as an unmet medical need.

Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity : Case report and literature review.

BACKGROUND: In general, late side effects after salvage radiotherapy (RT) for prostate cancer are below 10%. Patients with impaired DNA repair ability and genetic instability can have significantly increased reactions after RT. CASE, CLINICAL FOLLOW-UP, AND EXAMINATION: We present a patient who experienced severe side effects after additive RT for prostate cancer and died from the complications 25 months after RT. Imaging (MR) is shown as well as three-color fluorescence in situ hybridization. The blood sample testing revealed that radiosensitivity was increased by 35-55%. We undertook a review of the literature to give an overview over the tests established that are currently considered useful. CONCLUSION: This case highlights that the identification of patients with increased radiosensitivity is an important task in radiation protection. Groups of patients who should be screened have to be found and corresponding research facilities have to be set up.

[Callus distraction and bone transport in the treatment of bone defects]. / Kallusdistraktion und Segmenttransport zur Behandlung von Knochendefekten.

BACKGROUND: The method of "callus distraction" is the only technique which spontaneously produces vascularized bone within the surrounding soft tissues during lengthening reconstructive procedures. Remodeling of the regenerate bone to specific mechanical load can be influenced by the surgeon. In principle, there is no limit to the amount of new bone formation which can be created; this vascularized bone is both resistant to infection and can be created to replace resected infected bone. This is an important prerequisite for the successful treatment of large bone defects. TECHNIQUE: The ring fixator is still a standard tool if no radiological control is available in the operating theater, or in other less sophisticated environments. Over the last 30 years, however, the development of motorized, external and fully implantable systems has made it possible to achieve a significant increase in device implementation, which goes far beyond the standard. RESULTS: High-performance, reliable, custom-made external and fully implantable systems are cost intensive and require special surgical skills, which can only be ensured at specialized centers. However, the complication-free treatment results justify the effort both for the patient and, ultimately, for the cost bearers.

Neurological Deficits of an Rps19(Arg67del) Model of Diamond-Blackfan Anaemia.

Diamond-Blackfan anaemia is a rare disease caused by insufficient expression of ribosomal proteins and is characterized by erythroid hypoplasia often accompanied by growth retardation, congenital craniofacial and limb abnormalities. In addition, Diamond-Blackfan anaemia patients also exhibit a number of behavioural abnormalities. In this study we describe the behavioural effects observed in a new mouse mutant carrying a targeted single amino acid deletion in the ribosomal protein RPS19. This mutant, created by the deletion of arginine 67 in RPS19, exhibits craniofacial, skeletal, and brain abnormalities, accompanied by various neurobehavioural malfunctions. A battery of behavioural tests revealed a moderate cognitive impairment and neuromuscular dysfunction resulting in profound gait abnormalities. This novel Rps19 mutant shows behavioural phenotypes resembling that of the human Diamond-Blackfan anaemia syndrome, thus creating the possibility to use this mutant as a unique murine model for studying the molecular basis of ribosomal protein deficiencies.

Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients.

BACKGROUND: Recent evidence suggests that ionizing radiation may be associated with unexpected side-effects in melanoma patients treated with concomitant BRAF inhibitors. A large multicenter analysis was carried out to generate reliable safety data and elucidate the mechanism. METHODS: A total of 161 melanoma patients from 11 European skin cancer centers were evaluated for acute and late toxicity, of whom 70 consecutive patients received 86 series of radiotherapy with concomitant BRAF inhibitor therapy. To further characterize and quantify a possible radiosensitization by BRAF inhibitors, blood samples of 35 melanoma patients were used for individual radiosensitivity testing by fluorescence in situ hybridization of chromosomal breaks after ex vivo irradiation. RESULTS: With radiotherapy and concomitant BRAF inhibitor therapy the rate of acute radiodermatitis ≥2° was 36% and follicular cystic proliferation was seen in 13% of all radiotherapies. Non-skin toxicities included hearing disorders (4%) and dysphagia (2%). Following whole-brain radiotherapy, rates of radiodermatitis ≥2° were 44% and 8% (P < 0.001) for patients with and without BRAF inhibitor therapy, respectively. Concomitant treatment with vemurafenib induced acute radiodermatitis ≥2° more frequently than treatment with dabrafenib (40% versus 26%, P = 0.07). In line with these findings, analysis of chromosomal breaks ex vivo indicated significantly increased radiosensitivity for patients under vemurafenib (P = 0.004) and for patients switched from vemurafenib to dabrafenib (P = 0.002), but not for patients on dabrafenib only. No toxicities were reported after stereotactic treatment. CONCLUSION: Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.

Dynamics of water-alcohol mixtures: insights from nuclear magnetic resonance, broadband dielectric spectroscopy, and triplet solvation dynamics.

We combine (2)H nuclear magnetic resonance (NMR), broadband dielectric spectroscopy (BDS), and triplet solvation dynamics (TSD) to investigate molecular dynamics in glass-forming mixtures of water and propylene glycol in very broad time and temperature ranges. All methods yield consistent results for the α process of the studied mixtures, which hardly depends on the composition and shows Vogel-Fulcher temperature dependence as well as Cole-Davidson spectral shape. The good agreement between BDS and TDS data reveals that preferential solvation of dye molecules in microheterogeneous mixtures does not play an important role. Below the glass transition temperature T(g), NMR and BDS studies reveal that the ß process of the mixtures shows correlation times, which depend on the water concentration, but exhibit a common temperature dependence, obeying an Arrhenius law with an activation energy of E(a) = 0.54 eV, as previously reported for mixtures of water with various molecular species. Detailed comparison of NMR and BDS correlation functions for the ß process unravels that the former decay faster and more stretched than the latter. Moreover, the present NMR data imply that propylene glycol participates in the ß process and, hence, it is not a pure water process, and that the mechanism for molecular dynamics underlying the ß process differs in mixtures of water with small and large molecules.

Intranasal trigeminal sensitivity: measurements before and after nasal surgery.

Nasal surgeries constitute an extensive manipulation of the nasal mucosa and therefore of structures related to trigeminal and olfactory sensitivity. While olfactory changes due to nasal surgery are relatively well investigated, there are only very few studies regarding trigeminal sensitivity. Aim of the present study was to investigate sensory changes after nasal surgery with special regard to the trigeminal sensitivity. In 38 patients prior to and around 12 weeks after nasal surgery the following psychophysical measures were performed: odor identification, odor discrimination, phenyl ethyl alcohol odor threshold, sensitivity to trigeminal stimuli, trigeminal detection thresholds and trigeminal pain thresholds. These results were compared to those of a control group (43 healthy volunteers). Psychophysical olfactory and trigeminal testing showed no major changes in patients after surgery compared to the control group. Independent from the time of measurement higher trigeminal detection thresholds were found in patients compared to healthy subjects, meaning that trigeminal thresholds were already increased before surgery. The present study revealed a decreased trigeminal sensitivity in patients already before surgery. It may be hypothesized that patients also exhibit a decreased sensitivity for nasal airflow, which may also contribute to the patients' impression of impaired nasal breathing.

[Strategies in the treatment of supracondylar fractures of the humerus in children - proven and controversial]. / Behandlungsstrategien bei der suprakondylären Humerusfraktur im Kindesalter - Bewährtes und Kontroverses.

Elbow fractures are the 2nd most frequent fractures in children. Their therapy needs high expertise. Particularly an adequate analgesic therapy as well as an efficient and differentiated non-surgical or surgical therapy depending on the fracture type needs to be chosen. Secondary damage, especially growth disturbances, has to be prevented. Type I fractures can be managed conservatively with a cast. The crossed percutaneous pin fixation after open or closed reduction is the typical and most frequent surgical treatment option in supracondylar humeral fractures in children. Another good treatment option for supracondylar fractures type II to IV after closed reduction is the elastic-stable intramedullar nailing (ESIN). It is a minimally invasive treatment away from the fracture zone, which allows immediate free movement of the extremity. An immobilisation in a cast is therefore not necessary. That are the most possible effects (opinion of the authors) of the ESIN method, but discussed controversial in the literature. Especially neurovascular concomitant injuries require a differentiated treatment strategy to prevent long-term damage and should only be carried out in a specialised paediatric surgery unit. Long-term complications of supracondylar fractures are limitations in range of motion, nerval palsies, disturbances of growth, as well as cubitus varus (30 %) and valgus (3-7 %). These last ones often result from an insufficient initial anatomic reduction. The aim of the therapy should in any case be a patient-orientated treatment with the expected quickest recovery time and lowest long-term complications. Therefore supracondylar fractures should be treated only by a specialised paediatric trauma team, which can provide all non-surgical and surgical treatments. The spontaneous correcture is only seen in the sagittal view in young children between 6-7 years of age.

In vivo corrosion, tumor outcome, and microarray gene expression for two types of muscle-implanted tungsten alloys.

Tungsten alloys are composed of tungsten microparticles embedded in a solid matrix of transition metals such as nickel, cobalt, or iron. To understand the toxicology of these alloys, male F344 rats were intramuscularly implanted with pellets of tungsten/nickel/cobalt, tungsten/nickel/iron, or pure tungsten, with tantalum pellets as a negative control. Between 6 and 12 months, aggressive rhabdomyosarcomas formed around tungsten/nickel/cobalt pellets, while those of tungsten/nickel/iron or pure tungsten did not cause cancers. Electron microscopy showed a progressive corrosion of the matrix phase of tungsten/nickel/cobalt pellets over 6 months, accompanied by high urinary concentrations of nickel and cobalt. In contrast, non-carcinogenic tungsten/nickel/iron pellets were minimally corroded and urinary metals were low; these pellets having developed a surface oxide layer in vivo that may have restricted the mobilization of carcinogenic nickel. Microarray analysis of tumors revealed large changes in gene expression compared with normal muscle, with biological processes involving the cell cycle significantly up-regulated and those involved with muscle development and differentiation significantly down-regulated. Top KEGG pathways disrupted were adherens junction, p53 signaling, and the cell cycle. Chromosomal enrichment analysis of genes showed a highly significant impact at cytoband 7q22 (chromosome 7) which included mouse double minute (MDM2) and cyclin-dependant kinase (CDK4) as well as other genes associated with human sarcomas. In conclusion, the tumorigenic potential of implanted tungsten alloys is related to mobilization of carcinogenic metals nickel and cobalt from corroding pellets, while gene expression changes in the consequent tumors are similar to radiation induced animal sarcomas as well as sporadic human sarcomas.

Validation of the International Trauma Questionnaire-Child and Adolescent Version (ITQ-CA) in a Chinese mental health service seeking adolescent sample.

BACKGROUND: The International Trauma Questionnaire-Child and Adolescent version (ITQ-CA) is a self-report measure that assesses posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) based on the diagnostic formulation of the 11th version of the International Classification of Diseases (ICD-11). This study aimed to provide a Chinese translation and psychometric evaluation of the ITQ-CA using a sample of mental-health service seeking adolescents in Mainland China. METHODS: The ITQ-CA was translated and back-translated from English to simplified Chinese and finalized with consensus from an expert panel. Adolescents ages 12-17 were recruited via convenience sampling from an outpatient psychiatric clinic in Mainland China. Participants completed the ITQ-CA; measures of four criterion variables (depression, anxiety, stress, adverse childhood experiences); and the PTSD Checklist for DSM-5 (PCL-5). Construct validity, concurrent validity, and comparison of PTSD caseness between ICD-11 and DSM-5 measures were assessed. RESULTS: The final sample consisted of 111 Chinese adolescents (78% female; mean age of 15.23), all diagnosed with a major depressive disorder. Confirmatory factor analysis indicated the two-factor second-order model provided optimal fit. All criterion variables were positively and significant correlated with the six ITQ-CA symptom cluster summed scores. In the present sample, 69 participants (62.16%) met symptom criteria for ICD-PTSD or CPTSD using the ITQ-CA, and 73 participants (65.77%) met caseness for DSM-5 PTSD using the PCL-5. Rates of PTSD symptom cluster endorsement and caseness deriving from both diagnostic systems were comparable. CONCLUSIONS: The Chinese ITQ-CA has acceptable psychometric properties and confers additional benefits in identifying complex presentations of trauma-related responses in younger people seeking mental health services.